Presentation is loading. Please wait.

Presentation is loading. Please wait.

Doxycycline inhibition of aneurysmal degeneration in an elastase-induced rat model of abdominal aortic aneurysm: Preservation of aortic elastin associated.

Published byΜίνως Αβραμίδης Modified over 5 years ago

Similar presentations

Presentation on theme: "Doxycycline inhibition of aneurysmal degeneration in an elastase-induced rat model of abdominal aortic aneurysm: Preservation of aortic elastin associated."— Presentation transcript:

1 Doxycycline inhibition of aneurysmal degeneration in an elastase-induced rat model of abdominal aortic aneurysm: Preservation of aortic elastin associated with suppressed production of 92 kD gelatinase  Drazen Petrinec, MD, Shixiong Liao, MS, Dennis R. Holmes, MD, Jeffrey M. Reilly, MD, William C. Parks, PhD, Robert W. Thompson, MD  Journal of Vascular Surgery  Volume 23, Issue 2, Pages (February 1996) DOI: /S (96) Copyright © 1996 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

2 Fig. 1 Comparison of rat aortic diameter after elastase perfusion and treatment with either doxycycline or saline solution. Data shown are mean ± SEM of aortic diameter for animals in each group (n = 6). Open circles, doxycycline-treated rats; closed squares, saline solution-treated control group. Abdominal aortic aneurysm, defined as increase in aortic diameter to at least twice that of preperfusion control, is indicated by dashed line. *Significant difference between doxycycline- and saline solution-treated groups (p < 0.01, Student's t test). Journal of Vascular Surgery  , DOI: ( /S (96) ) Copyright © 1996 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

3 Fig. 2 Histologic appearance of rat aorta at various intervals after elastase perfusion and treatment with saline solution or doxycycline. Elastase perfusion causes little detectable damage to elastic lamellae (arrows) up to 2 days (B). In saline solution-treated control group with aneurysmal dilatation, pronounced elastin degradation occurs by day 7 (C), associated with dense inflammatory response, which is resolved by day 14 (E). In contrast, elastic lamellae are preserved in nonaneurysmal doxycycline-treated rats both at 7 days (D) and 14 days (F), in spite of occurrence of inflammatory response similar to that seen in control group. At 14 days, outer aortic wall of doxycycline-treated rats is thicker, with more collagenous fibrosis, than that seen in saline solution-treated control group. (Verhoff-van Giesen stain, original magnification × 100) Journal of Vascular Surgery  , DOI: ( /S (96) ) Copyright © 1996 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

4 Fig. 2 Histologic appearance of rat aorta at various intervals after elastase perfusion and treatment with saline solution or doxycycline. Elastase perfusion causes little detectable damage to elastic lamellae (arrows) up to 2 days (B). In saline solution-treated control group with aneurysmal dilatation, pronounced elastin degradation occurs by day 7 (C), associated with dense inflammatory response, which is resolved by day 14 (E). In contrast, elastic lamellae are preserved in nonaneurysmal doxycycline-treated rats both at 7 days (D) and 14 days (F), in spite of occurrence of inflammatory response similar to that seen in control group. At 14 days, outer aortic wall of doxycycline-treated rats is thicker, with more collagenous fibrosis, than that seen in saline solution-treated control group. (Verhoff-van Giesen stain, original magnification × 100) Journal of Vascular Surgery  , DOI: ( /S (96) ) Copyright © 1996 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

5 Fig. 2 Histologic appearance of rat aorta at various intervals after elastase perfusion and treatment with saline solution or doxycycline. Elastase perfusion causes little detectable damage to elastic lamellae (arrows) up to 2 days (B). In saline solution-treated control group with aneurysmal dilatation, pronounced elastin degradation occurs by day 7 (C), associated with dense inflammatory response, which is resolved by day 14 (E). In contrast, elastic lamellae are preserved in nonaneurysmal doxycycline-treated rats both at 7 days (D) and 14 days (F), in spite of occurrence of inflammatory response similar to that seen in control group. At 14 days, outer aortic wall of doxycycline-treated rats is thicker, with more collagenous fibrosis, than that seen in saline solution-treated control group. (Verhoff-van Giesen stain, original magnification × 100) Journal of Vascular Surgery  , DOI: ( /S (96) ) Copyright © 1996 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

6 Fig. 2 Histologic appearance of rat aorta at various intervals after elastase perfusion and treatment with saline solution or doxycycline. Elastase perfusion causes little detectable damage to elastic lamellae (arrows) up to 2 days (B). In saline solution-treated control group with aneurysmal dilatation, pronounced elastin degradation occurs by day 7 (C), associated with dense inflammatory response, which is resolved by day 14 (E). In contrast, elastic lamellae are preserved in nonaneurysmal doxycycline-treated rats both at 7 days (D) and 14 days (F), in spite of occurrence of inflammatory response similar to that seen in control group. At 14 days, outer aortic wall of doxycycline-treated rats is thicker, with more collagenous fibrosis, than that seen in saline solution-treated control group. (Verhoff-van Giesen stain, original magnification × 100) Journal of Vascular Surgery  , DOI: ( /S (96) ) Copyright © 1996 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

7 Fig. 2 Histologic appearance of rat aorta at various intervals after elastase perfusion and treatment with saline solution or doxycycline. Elastase perfusion causes little detectable damage to elastic lamellae (arrows) up to 2 days (B). In saline solution-treated control group with aneurysmal dilatation, pronounced elastin degradation occurs by day 7 (C), associated with dense inflammatory response, which is resolved by day 14 (E). In contrast, elastic lamellae are preserved in nonaneurysmal doxycycline-treated rats both at 7 days (D) and 14 days (F), in spite of occurrence of inflammatory response similar to that seen in control group. At 14 days, outer aortic wall of doxycycline-treated rats is thicker, with more collagenous fibrosis, than that seen in saline solution-treated control group. (Verhoff-van Giesen stain, original magnification × 100) Journal of Vascular Surgery  , DOI: ( /S (96) ) Copyright © 1996 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

8 Fig. 2 Histologic appearance of rat aorta at various intervals after elastase perfusion and treatment with saline solution or doxycycline. Elastase perfusion causes little detectable damage to elastic lamellae (arrows) up to 2 days (B). In saline solution-treated control group with aneurysmal dilatation, pronounced elastin degradation occurs by day 7 (C), associated with dense inflammatory response, which is resolved by day 14 (E). In contrast, elastic lamellae are preserved in nonaneurysmal doxycycline-treated rats both at 7 days (D) and 14 days (F), in spite of occurrence of inflammatory response similar to that seen in control group. At 14 days, outer aortic wall of doxycycline-treated rats is thicker, with more collagenous fibrosis, than that seen in saline solution-treated control group. (Verhoff-van Giesen stain, original magnification × 100) Journal of Vascular Surgery  , DOI: ( /S (96) ) Copyright © 1996 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

9 Fig. 3 Cellular infiltration of rat aortic media 7 days after elastase-perfusion and treatment with saline solution (A and B) or doxycycline (C and D). Destruction of elastic lamellae is seen adjacent to infiltrating inflammatory cells in saline solution-treated control group, whereas elastic lamellae adjacent to inflammatory cells are preserved in animals treated with doxycycline. A and C, Verhoff-van Giesen stain, B and D, hematoxylin-eosin stain. (Original magnification ×200). Journal of Vascular Surgery  , DOI: ( /S (96) ) Copyright © 1996 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

10 Fig. 3 Cellular infiltration of rat aortic media 7 days after elastase-perfusion and treatment with saline solution (A and B) or doxycycline (C and D). Destruction of elastic lamellae is seen adjacent to infiltrating inflammatory cells in saline solution-treated control group, whereas elastic lamellae adjacent to inflammatory cells are preserved in animals treated with doxycycline. A and C, Verhoff-van Giesen stain, B and D, hematoxylin-eosin stain. (Original magnification ×200). Journal of Vascular Surgery  , DOI: ( /S (96) ) Copyright © 1996 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

11 Fig. 3 Cellular infiltration of rat aortic media 7 days after elastase-perfusion and treatment with saline solution (A and B) or doxycycline (C and D). Destruction of elastic lamellae is seen adjacent to infiltrating inflammatory cells in saline solution-treated control group, whereas elastic lamellae adjacent to inflammatory cells are preserved in animals treated with doxycycline. A and C, Verhoff-van Giesen stain, B and D, hematoxylin-eosin stain. (Original magnification ×200). Journal of Vascular Surgery  , DOI: ( /S (96) ) Copyright © 1996 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

12 Fig. 3 Cellular infiltration of rat aortic media 7 days after elastase-perfusion and treatment with saline solution (A and B) or doxycycline (C and D). Destruction of elastic lamellae is seen adjacent to infiltrating inflammatory cells in saline solution-treated control group, whereas elastic lamellae adjacent to inflammatory cells are preserved in animals treated with doxycycline. A and C, Verhoff-van Giesen stain, B and D, hematoxylin-eosin stain. (Original magnification ×200). Journal of Vascular Surgery  , DOI: ( /S (96) ) Copyright © 1996 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

13 Fig. 4 Comparison of enzymatic activities after elastase perfusion and treatment with saline solution (Sal) or doxycycline (Dox). Protein-normalized aortic extracts from unperfused rats (Pre) and elastase-perfused rats killed at 2, 7, or 14 days were examined by substrate zymography with gelatin (A) or casein (B) substrates. Control group included A, mixture of authentic human 92 and 72 kD gelatinases (92/72), and B, porcine pancreatic elastase (PPE). Journal of Vascular Surgery  , DOI: ( /S (96) ) Copyright © 1996 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

14 Fig. 4 Comparison of enzymatic activities after elastase perfusion and treatment with saline solution (Sal) or doxycycline (Dox). Protein-normalized aortic extracts from unperfused rats (Pre) and elastase-perfused rats killed at 2, 7, or 14 days were examined by substrate zymography with gelatin (A) or casein (B) substrates. Control group included A, mixture of authentic human 92 and 72 kD gelatinases (92/72), and B, porcine pancreatic elastase (PPE). Journal of Vascular Surgery  , DOI: ( /S (96) ) Copyright © 1996 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

15 Fig. 5 Relative density of 92 kD gelatinase (A) and 72 kD gelatinase (B) activities extracted from saline solution- and doxycycline-treated rat aortas at various intervals after elastase perfusion. For each gelatin-degrading band quantitated by densitometry of representative zymogram, relative density is expressed as percent of day-0 control. Journal of Vascular Surgery  , DOI: ( /S (96) ) Copyright © 1996 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

16 Fig. 5 Relative density of 92 kD gelatinase (A) and 72 kD gelatinase (B) activities extracted from saline solution- and doxycycline-treated rat aortas at various intervals after elastase perfusion. For each gelatin-degrading band quantitated by densitometry of representative zymogram, relative density is expressed as percent of day-0 control. Journal of Vascular Surgery  , DOI: ( /S (96) ) Copyright © 1996 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

17 Fig. 6 Effect of doxycycline on rat aortic gelatinase activities in vitro. A, Aortic extract from 7-day saline solution-treated animal in control group was mixed with doxycycline and analyzed by gelatin zymography. No inhibition of gelatinase activities by doxycycline is observed at any concentration tested. B, Control aortic extract used in A was resolved by electrophoresis through gel containing gelatin substrate, and each lane was incubated in separate substrate buffers supplemented with doxycycline. Mild inhibition of both 92 kD and 72 kD gelatinase activities is observed at exogenous doxycycline concentrations of 20 μm. Journal of Vascular Surgery  , DOI: ( /S (96) ) Copyright © 1996 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

18 Fig. 6 Effect of doxycycline on rat aortic gelatinase activities in vitro. A, Aortic extract from 7-day saline solution-treated animal in control group was mixed with doxycycline and analyzed by gelatin zymography. No inhibition of gelatinase activities by doxycycline is observed at any concentration tested. B, Control aortic extract used in A was resolved by electrophoresis through gel containing gelatin substrate, and each lane was incubated in separate substrate buffers supplemented with doxycycline. Mild inhibition of both 92 kD and 72 kD gelatinase activities is observed at exogenous doxycycline concentrations of 20 μm. Journal of Vascular Surgery  , DOI: ( /S (96) ) Copyright © 1996 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

Download ppt "Doxycycline inhibition of aneurysmal degeneration in an elastase-induced rat model of abdominal aortic aneurysm: Preservation of aortic elastin associated."

Similar presentations

Age of onset, pattern of distribution, and histology of aneurysm development in a genetically predisposed mouse model  Colleen M. Brophy, MD, Joan E.

Age of onset, pattern of distribution, and histology of aneurysm development in a genetically predisposed mouse model  Colleen M. Brophy, MD, Joan E.
Elastin, collagen, and some mechanical aspects of arterial aneurysms

Elastin, collagen, and some mechanical aspects of arterial aneurysms
Mesenchymal stem cells attenuate angiotensin II-induced aortic aneurysm growth in apolipoprotein E-deficient mice  Ryotaro Hashizume, MD, Aika Yamawaki-Ogata,

Mesenchymal stem cells attenuate angiotensin II-induced aortic aneurysm growth in apolipoprotein E-deficient mice  Ryotaro Hashizume, MD, Aika Yamawaki-Ogata,
Elastic fibers reconstructed using adenovirus-mediated expression of tropoelastin and tested in the elastase model of abdominal aortic aneurysm in rats 

Elastic fibers reconstructed using adenovirus-mediated expression of tropoelastin and tested in the elastase model of abdominal aortic aneurysm in rats 
Endogenous superoxide dismutase activation by oral administration of riboflavin reduces abdominal aortic aneurysm formation in rats  Zhenhai Yu, MD, Keisuke.

Endogenous superoxide dismutase activation by oral administration of riboflavin reduces abdominal aortic aneurysm formation in rats  Zhenhai Yu, MD, Keisuke.
Coarctation-induced degenerative abdominal aortic aneurysm in a porcine model  Pao-Yen Lin, MD, Yeng-Ting Wu, MS, Guan-Cheng Lin, BS, Yao Hsiang Shih,

Coarctation-induced degenerative abdominal aortic aneurysm in a porcine model  Pao-Yen Lin, MD, Yeng-Ting Wu, MS, Guan-Cheng Lin, BS, Yao Hsiang Shih,
Christopher K. Zarins, MD, Chengpei Xu, MD, Seymour Glagov, MD 

Christopher K. Zarins, MD, Chengpei Xu, MD, Seymour Glagov, MD 
Chang M. He, MSc, Margot R. Roach, MD, PhD  Journal of Vascular Surgery 

Chang M. He, MSc, Margot R. Roach, MD, PhD  Journal of Vascular Surgery 
Wanfen Xiong, PhD, Rebecca A. Knispel, BS, Harry C

Wanfen Xiong, PhD, Rebecca A. Knispel, BS, Harry C
Loss of STAT1 is associated with increased aortic rupture in an experimental model of aortic dissection and aneurysm formation  Matthew J. Eagleton, MD,

Loss of STAT1 is associated with increased aortic rupture in an experimental model of aortic dissection and aneurysm formation  Matthew J. Eagleton, MD,
Tamoxifen up-regulates catalase production, inhibits vessel wall neutrophil infiltration, and attenuates development of experimental abdominal aortic.

Tamoxifen up-regulates catalase production, inhibits vessel wall neutrophil infiltration, and attenuates development of experimental abdominal aortic.
Effect of blocking platelet activation with AZD6140 on development of abdominal aortic aneurysm in a rat aneurysmal model  Jianping Dai, MD, PhD, Liliane.

Effect of blocking platelet activation with AZD6140 on development of abdominal aortic aneurysm in a rat aneurysmal model  Jianping Dai, MD, PhD, Liliane.
Infection of vascular prostheses caused by bacterial biofilms

Infection of vascular prostheses caused by bacterial biofilms
Gorav Ailawadi, MD, Christopher W. Moehle, BS, Hong Pei, MD, Sandra P

Gorav Ailawadi, MD, Christopher W. Moehle, BS, Hong Pei, MD, Sandra P
Controlled release of ascorbic acid from gelatin hydrogel attenuates abdominal aortic aneurysm formation in rat experimental abdominal aortic aneurysm.

Controlled release of ascorbic acid from gelatin hydrogel attenuates abdominal aortic aneurysm formation in rat experimental abdominal aortic aneurysm.
Mark Wengrovitz, MD. , Lulseged G. Selassie, MD. , Robert R. M

Mark Wengrovitz, MD. , Lulseged G. Selassie, MD. , Robert R. M
Suppression of experimental abdominal aortic aneurysms in mice by treatment with pyrrolidine dithiocarbamate, an antioxidant inhibitor of nuclear factor-κB 

Suppression of experimental abdominal aortic aneurysms in mice by treatment with pyrrolidine dithiocarbamate, an antioxidant inhibitor of nuclear factor-κB 
Journal of Vascular Surgery

Journal of Vascular Surgery
Indomethacin inhibits expansion of experimental aortic aneurysms via inhibition of the cox2 isoform of cyclooxygenase  Manuel Miralles, MD, William Wester,

Indomethacin inhibits expansion of experimental aortic aneurysms via inhibition of the cox2 isoform of cyclooxygenase  Manuel Miralles, MD, William Wester,
Orally administered dipeptidyl peptidase-4 inhibitor (alogliptin) prevents abdominal aortic aneurysm formation through an antioxidant effect in rats 

Orally administered dipeptidyl peptidase-4 inhibitor (alogliptin) prevents abdominal aortic aneurysm formation through an antioxidant effect in rats 

Similar presentations

Ads by Google